Phase II PI drug trial - comments?

[Trish77]

This is the drug trial I'm being screened for currently.  I will find out in two weeks.  If I get in, things will move VERY fast as last date for first dose is March 3rd and likely will be before that.  

I've seen others comment on how their own drug trials demanded some level of secrecy on the part of the participants so I asked about that .. and there are no demands of me in that regard.  

I'd be interested in any comments - positive, negative, "are ya nuts?" variety....doesn't matter.  Don't hold back now.  :)

http://clinicaltrials.gov/ct2/show/NCT00517439?term=hepatitis+toronto&rank=42

Thanks.

Trish

[Trish77]

It's almost like an adventure from the point of view of sailing into the unknown, and it's ok except for when you feel like cr@p.
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Well....I always have been a sucker for an adventure.  I guess I will see, eh?

[dointime]

"They did tell me that the main risk factor with the Pro-Drug is plummeting WBC count.  I will have to ask how they monitor and make sure I know what to watch for, if I get in."

It's all from the blood tests.  I had a look at my old blood results.  There is a value for WBC but the important one is the reading for neutrophils.  You'll soon find out which values are considered relevant by the frowns and oohs and aahs of the doc.  It's almost like an adventure from the point of view of sailing into the unknown, and it's ok except for when you feel like cr@p.

dointime  

  

[Trish77]

mikesimon:  Thanks again for posting that information.  It sent me on a bit of a reading spree.  That 78%ile of those who got Grade 4 Neutropenia was found to be in those that received the 3000mg dose of R1626 and that might explain why none of the arms go above 1500mg.  I did end up reading up much more on neutropenia than I might have otherwise and thanks for opening my eyes that much more. Very useful.

Three arms at 500mg, 1000mg and 1500mg for 24 weeks + SOC and then 24 weeks of SOC only.  Three arms of 500mg, 1000mg, 1500mg + 90mg INF and SOC riba for 24, then 24 weeks of SOC.  One of thoses arms will be 500mg + SOC for 24 weeks and if you RVR, you're done at 24.   And then one comparative of regular SOC for 48 weeks.

They did tell me that the main risk factor with the Pro-Drug is plummeting WBC count.  I will have to ask how they monitor and make sure I know what to watch for, if I get in.

LL:  Thanks for your words.  I don't know the answer to your trial questions as I'm very new.  All I know for myself, is that I had no intention of signing if I wasn't good with following through on any of the arms.  And I signed.  So now I wait.  And yes...I'm more than ready to proceed and I suppose that is one of the bonuses of the drug trial.  My wait comes to an abrupt end.  The other is the opportunity to have R1626 added to my tx.  For a geno 1 with our odds...I at least have a shot at a better SVR outcome if I grab the right arm.  Without the drug trial, I have NO shot at it and it's regular SOC and tweak where I can.  That isn't bad either...but this seemed like a good calculated risk.  Yes, Phase III's do seem like the better option but...there isn't one available to me and as I keep saying...I'm not waiting any longer to do tx.  

Oneeagle...you're a pioneer. :)  Thanks for the encouragement and congrats on your SVR!!!!

MerryBe..thanks for the info.  I will be keeping an eye on me along with them keeping an eye on me. :)  I have an appointment with my family doc this Thursday and I'll fill him in on what's going on so that if I end up having any problems he'll already know what's going on.  My hep docs are out of Toronto and that's an hour away so some local backup is good.

Dointime......thank you.  Thank you for all your comments and your quiet support.  Now...I just wait.  Not very patiently..but I wait.

Jim ... I hear you on whether to get in now or wait.  And I imagine you've heard me on what I think of waiting. :)  Thanks for the input and the information.  Invaluable.

I'll post once I know.  Thanks all.

Trish

[Trish77]

I just wanted to thank everyone for their input....I haven't had time to do anything other than read...digest...and read some more, in amongst the other things in life.  

mikesimon, thanks for that post.  That probably got me reading the most and is a bit of sobering yet necessary information.  Thanks.

[merryBe]

well, I got the big bone marrow suppresion discussion going the other day as we discussed my absrption effecting CBC"S.
apparently the reasoning for  trying to avoid need for recue drugs and/or transfusion is bound up in how able the patient can be matched at a later date to a liver.
the sides aside, epo/neupo etc mess with the marrow and immune system, and transfusions create  so many new antibodies to foreign blood...that in both cases they find recipients that have these procedures far more likely to develop antibodies and reject any donor organ.
So I stand corrected. I thought it was just the expense making dcs shy away from tx f this type, but evidently part f the stategy is t try t kill the virus but leave your immune system intact enough to handle a transplant shuld that prove your best best.
just thought I'd thrw this in the mix.
Good luck with your trials.   By right you are allowed to see your labs. If yu get too sick they are supposed to just discontinue you, but that may be quite sick, and you ahould have a right to knw if yur blood has tanked as there are risks to doing nothing just as t using the rescue drugs.

[dointime]

Trish, your definition of double-blind is absolutely correct and thanks for pointing out my misconception.  Because the PCR results were witheld in my trial I assumed that that was part of the double blind - but it wasn't.  I guess Vertex just figured there would be less ship jumpers if we were kept ignorant of our VL, and they were right.

So I have to give Roche credit here because they are retaining the scientific method of the double-blind but being more humane and ethical (in my opinion) by keeping you informed of your VL so that you know if the tx is working.  dointime.

http://en.wikipedia.org/wiki/Double-blind

"In a double-blind experiment, neither the individuals nor the researchers know who belongs to the control group and the experimental group. Only after all the data has been recorded (and in some cases, analyzed) do the researchers learn which individuals are which. Performing an experiment in double-blind fashion is a way to lessen the influence of the prejudices and unintentional physical cues on the results (the placebo effect, observer bias, and experimenter's bias). Random assignment of the subject to the experimental or control group is a critical part of double-blind research design. The key that identifies the subjects and which group they belonged to is kept by a third party and not given to the researchers until the study is over."

[jmjm530]

From Afdhal, above: hus, R1626 clearly had a significant bone marrow–suppressing adverse effect, with the incidence of grade 4 neutropenia ranging from 39% to 78%.
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Grade 4 would be ANC below 500, although how far below in percentage populations is not stated here but no doubt available. As Dr. J. states, low ANC does not seem to be the concern it once was, however "how low can you go" is the question. My docs allowed me to stay on full-dose Peg at ANC 320 without Neupogen and probably would not hv intervened unless it stayed around 300 for several weeks which it didn't and in fact rebounded by itself, which may not happen with this new drug. This also brings up the Neupogen issue and why -- if it isn't -- being used in the study as for example in an additional arm (make that 8 whew) where full dose Peg is used with Neupogen allowed, as opposed to an arm where full dose Peg is used without Neupogen.

Trish, from your point of view the variables seem not just the drug itself but what arm you end up in and how that arm turns out, esp if it turns out that full dose peg turns out to be necessary.

Certainly sound promising and folks just have to decide whether they want to get in at this early stage or perhaps wait until some of these questions are answered in the current trial.

-- Jim

[oneeagle]

I was in first trial at Mayo to establish inerferon/ribavarin therapy in 1995 - I would love to hear a synopsis of new approaches - I have been viral clear since my tx - but still am interested - and have fibrosis and other liver things to look at. My trial was 5 million units alpha interferon and trial amount of ribavarin. Riba daily and intrfrn every other day for a year. Have only lurked on this forum -mostly over on social addiction since I started doing too many narcs for comfort during therapy!!! Hang in there folks - I regret nothing about my choice and participation in trial.

[Lady Lauri]

Can't contribute much here, but the trial I am in I have never been told anything about 'secrecy', and someone pointed that out to me. I was never told a thing, so assuming not?

I was also in that 1st dose deadline, so was rushed in and luckily drew tha SOC, not the Albumin and thus far, there's problems with the dosing in it and serious lung issues with the albumin, their having to reduce, etc. As 2b tho, soc was good enough for me.

My opinion in trials is , unless time is a huge factor, damage is high, etc., to wait for phase 3 trials, as less risk, more info., stats, etc. It's a very unprofessional opinion tho!

Question: If one drew the short arm (wrong one they want) can they back out at that time and wait, or will it hurt them for future trials?

Once one has done a trial, didn't work, does it hurt their qualifications for next trials?

Figure it depends on each trial?

Good luck in your choice! I know your ready to go on this tx.

LL

[Trish77]

Thanks for this for a variety of reasons.  I had done a search looking for the list of articles presented at the AASLD 2007 because of one my NP referred to that I wanted to read and I couldn't find it for whatever reason.  Your link took me there.  I couldn't find the article relating to the topic she and I were discussing but I'm scanning and now I can go back later.

No congrats yet.  I'm in screening phase.  Still waiting to see if my long-ago HBV infection that cleared on it's own causes me grief.  I'm hoping not.  The study nurse didn't think so but we'll see.

I read the summary you posted.  This just simply adds to my sense that this is a good trial to be in and hoping I don't draw the short straw(s) but I'd rather take the chance than none at all.  Even the short straws on this one aren't too bad, seems to me.

[Trish77]

Jim,

Thanks for the links.  I've read and bookmarked them.  There are no teleprevir or boceprevir trials at the moment in this area, at least not according to clinicaltrials.gov.  There is one for teleprevir, however it's Phase II for non-responders to previous Teleprevir trials.  

The articles you posted actually make me feel a bit better about this.  I know 7 arms are alot of variables.  They seem to be studying multiple things with this one, one of which is SVR rates based on RVR for one of the arms.  

Incidentally, if I get in this trial, there is a sub-study taking place in conjunction with it that will study a variety of things and I'll be part of that too.  That's based more on various aspects of treatment and responses towards developing more appropriate treatment options.  I'll post specifics once I have the paperwork in front of me to do so clearly rather than from my feeble memory.  If I'm in the trial, I'm in the sub-study also.

[Trish77]

They told me it was doubleblind.  So perhaps I don't have my facts straight.  It IS doubleblind in that neither myself nor the trial sponsors will know which arm I'm in.

However, I WILL know the results of my quant PCR tests throughout the study.

Does this still mean doubleblind?

[dointime]

I started the phase II VX950 trial in January 2007, followed by SOC.  I've been off the meds now for about 6 months and feel almost normal again.

I think that somebody else here said that the trial was to be a double blind, so thanks for mentioning that it is actually unblinded.  That is so much better as it gives you many more choices if things are not going quite as you would wish.

Bear in mind that it is your right to drop out of the trial at any time if you believe that your tx needs can no longer be met within the trial protocol, for instance if you should need rescue drugs or wish to increase your interferon or ribavirin dose.  I'm not recommending you do this, heavens no, but it is your right.

dointime  

      

[Trish77]

Hi foo...yes, they told me that my response will be unblinded, as in I'll know all along the results of each VL test, if that's what you mean.

Good luck getting into Phase III of Teleprevir.  I just can't wait anymore.  Mentally, I have to do treatment like yesterday.  If I don't get into this drug trial I'm figuring I'll start regular SOC instead about the same time I would have started the trial.  That's my hope, if I don't get in.  I just can't wait anymore.

[Trish77]

Thanks for your comments.

I also think the arms with half dose interferon are the riskier ones and the only ones that give me concern. Thanks for commenting on that because I don't know as much as I'd like about INF. However, I'd be much more concerned about a lower dose of riba and all of these are weight-based.  Although...my original dosage was going to be 1400mg and I'll get 1200mg on this trial.  So...it's less than I'd like but still okay.  I'm doing it anyway and I'm hoping I don't draw the "short straw" but I knew I could and eyes wide open for the MOST part here.  Filling in some blanks between now and when I get the yay or nay.

How long ago did you do the Phase II VX950?  

I had Hep B in my late teens, very mild and it cleared on it's own.  The study nurse doesn't think that will disqualify.  I know one other person in the same boat who has been in plenty of drug trials so I should be okay but I'm waiting to see on that score.

[dointime]

I have a comment about some arms of this trial using half doses of interferon, ie. 90 micrograms pegasys instead of the normal 180.  

We do know already that R1626 can induce neutropenia and that this is the major reason for dose reductions and discontinuations.  We also know that interferon can cause neutropenia.  I am speculating that Roche are trying to mitigate the neutropenia problem by the dose reduction of interferon.  

I remember the VX950 trials when everybody said how great it would be if we could do away with the riba.  Well it would have been great except that it didn't work.  Now I'm thinking how great it would be if we could get away with a half dose of interferen - but will it work?  So I think that the half dose interferon arms are the riskier ones in this trial, from the point of view of efficacy.  

dointime      

[dointime]

This is the R1626 trial.  As Jim points out, we don't know a lot about this drug as yet, so you would be in the same position as anybody doing the first tranche of a phase 2 drug trial.

All I can tell you is that I was in that same early stage of the telaprevir drug trials.  At that stage, some of the arms will work and some might not.  I drew the short straw (the no-riba arm) and was not cured.  Others drew the triple therapy and went on to SVR.  So if you do the phase 2 trial then you just have to hope you'll be among the lucky ones.  A phase 3 trial is a lot better because the safety and efficacy are much better understood, so there's a better chance of getting something that will work.

So I guess it is down to your particular circumstances, and whether you want to roll the dice and take your chances with this trial, without knowing what your chances really are.  It's great that you are coming on here and keeping us informed about it.  

Best of luck,
dointime.    

        

[jmjm530]

Haven't heard of this drug but haven't been lately haven't been following newer drugs that closely. A quick search shows that it is being "fast tracked" which is interesting since Telaprevir isn't, as I understand it.

What I couldn't find are any SVR results, which would make me pause, esp if you had time to wait. On the other hand, Telaprevir does have some SVR results and other PI's (Boclavier (sp)?) should have them soon, I think.

Is your doc also tied into the Telaprevir trials? If so, you might ask for a comparision, i.e. why this drug over Telaprevir. . If not, you still might ask the same question, esp as to Telaprevir's track record compared to this drug. Also, since your doc seems connected with this new drug, you might inquire if it might make sense to wait out this phase and then jump in based on results. There are seven arms, so a lot of variables at this point.

Here are a few links and hopefully someone else can add more:

http://www.hivandhepatitis.com/hep_c/news/2006/101706_a.html
http://www.hivandhepatitis.com/2006icr/easl/docs/050206_c.html
http://www.natap.org/2006/AASLD/AASLD_13.htm

[foofighter]

Trial nurse and PA called me about this a couple of weeks ago, as they were very excited about great results they were seeing. I didn't take notes during the conversation so I don't have exactly what they said (the time frame) but I know they were jazzed about the drop in VL in a short time. Did you learn that your response is unblinded?

In another thread dointime had pointed out what I had posted wasn't so great, so I probably didn't get it right. I would hope it was sincere excitement and that they were not just trying to recruit me. Aquila has pointed out in a couple of threads that this trial has cut the Peg in half on some of the arms, which concerned me a bit.

I am holding out for the Phase 3 of Vertex, even though my PA mentioned there may be a Peg reduction in that trial as well. Don't know if that is true, but hopefully we will find out soon.

Ya never know...I may be sorry to have passed on trying to get into this trial. Anyway good luck on your path to SVR!